Dataset Information

The meta and bioinformatics analysis of GRP78 expression in gastric cancer.

ABSTRACT: GRP78 is a molecular chaperone located in endoplasmic reticulum, and induces folding and assembly of newly-synthesized proteins, proteasome degradation of aberrant proteins, and translocation of secretory proteins, autophagy, and epithelial-mesenchymal transition. We performed a systematic meta- and bioinformatics analysis through multiple online databases up to March 14, 2017. It was found that up-regulated GRP78 expression in gastric cancer, compared with normal mucosa at both protein and mRNA levels (p < 0.05). GRP78 expression was positively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer (p < 0.05), while its mRNA expression was negatively correlated with depth of invasion, histological grading and dedifferentiation (p < 0.05). A positive association between GRP78 expression and unfavorable overall survival was found in patients with gastric cancer (p < 0.005). A higher GRP78 mRNA expression was positively correlated with overall and progression-free survival rates of all cancer patients, even stratified by aggressive parameters, or as an independent factor (p < 0.05). These findings indicated that GRP78 expression might be employed as a potential marker to indicate gastric carcinogenesis and subsequent progression, even prognosis.

SUBMITTER: Zheng HC

PROVIDER: S-EPMC5641188 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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The meta and bioinformatics analysis of GRP78 expression in gastric cancer.

Zheng Hua-Chuan HC Gong Bao-Cheng BC Zhao Shuang S

Oncotarget 20170818 42

GRP78 is a molecular chaperone located in endoplasmic reticulum, and induces folding and assembly of newly-synthesized proteins, proteasome degradation of aberrant proteins, and translocation of secretory proteins, autophagy, and epithelial-mesenchymal transition. We performed a systematic meta- and bioinformatics analysis through multiple online databases up to March 14, 2017. It was found that up-regulated GRP78 expression in gastric cancer, compared with normal mucosa at both protein and mRNA ...[more]

PMID: 29069845

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Project description:BackgroundGastric cancer (GC) is one of the common gastrointestinal malignancy worldwide and exhibits a poor prognosis. Increasing studies have indicated that microRNAs play critical roles in the cancer progression and have shown great potential as useful biomarkers. The search for potential diagnostic and prognostic biomarkers of gastric cancer (GC) with integrated bioinformatics analyses has been undertaken in previous studies.MethodsIn this study, the robust rank aggregation (RRA) method was used to perform an integrated analysis of differentially expressed miRNAs (DEMs) from five microarray datasets in the Gene Expression Omnibus (GEO) database to find robust biomarkers for GC. Ultimately, seven miRNAs were filtered from fourteen primary miRNAs using the validation set of The Cancer Genome Atlas (TCGA) database. Based on these results, diagnostic and survival analyses were performed, and logistic regression and Cox regression were used to determine the clinicopathological characteristics of the DEM expression and overall survival.ResultsNine eligible miRNA datasets related to GC were selected from the GEO database for integrated analysis in this study. Diagnostic analysis implied that these miRNAs could be regarded as promising candidate diagnostic biomarkers in GC tissues, but whether the results of the tissue analysis are consistent with those of peripheral blood analysis requires further validation. The logistic regression indicated that the ectopic expression of these DEMs was relevant to the histological type, anatomical region, and pathological grade of GC. However, the survival and Cox regression analyses suggested that the poor prognosis of GC patients was not strongly dependent on the ectopic expression of the seven miRNAs, but rather, a poor prognosis was associated with age, metastasis, and histological grade.ConclusionsBased on the results presented in this study it can be concluded that these miRNAs (miR-455-3p, miR-135b-5p, let-7a-3p, miR-195-5p, miR-204-5p, miR-149-5p, and miR-143-3p) might be potential biomarkers for the early diagnosis of GC patients, but this finding should be regarded with caution. A large-scale, prospective, and multicenter cohort study should be performed.

Project description:PurposeGastric cancer (GC) is a common type of cancer worldwide. It can relapse and metastasize even after standard treatment; therefore, it has a poor prognosis. Moreover, sensitive biomarkers for prognosis prediction in GC are lacking. In this study, using a bioinformatics approach, we aimed to examine the value of DAZ Interacting Protein 1 (DZIP1) as a prognostic predictor and therapeutic target in GC.MethodsWe explored the clinical relevance, function, and molecular role of DZIP1 in GC using MethSurv, cBioPortal, TIMER, Gene Expression Profiling Interactive Analysis, IMEx, ONCOMINE, MEXPRESS, and EWAS Atlas databases. The GSE118919 dataset was used to plot receiver operating characteristic curves. Using The Cancer Genome Atlas, we developed a Cox regression model and assessed the clinical significance of DZIPs. In addition, we used the "xCELL" algorithm to make reliable immune infiltration estimations. Western blot and immunohistochemistry were used to examine protein expression. The results were visualized with the 'ggplot2' and "circlize" packages.ResultsIn GC patients, DZIP1 was over-expressed at both the mRNA and protein levels. High levels of DZIP1 were found to be associated with poor survival in patients with GC. Our results indicated that DZIP1 could be involved in multiple cancer-related pathways such as the PI3K-Akt signaling pathway, WNT signaling pathway, and RAS signaling pathway, and its expression was correlated with the infiltration of activated myeloid dendritic cells, naive CD4+ T cells, and naive CD8+ T cells. Furthermore, we found that mutations in DZIP1 were correlated with a good prognosis in GC patients. Finally, we demonstrated a correlation between hypomethylation of the DZIP1 gene promoter and a poor prognosis in GC.ConclusionThis study is the first to demonstrate a significant correlation between high levels of DZIP1 and a poor prognosis in GC patients. Our results clarify multiple potential mechanisms that could contribute to this correlation and may thus provide novel insights into the clinical diagnosis and treatment of GC.

Project description:Background: In addition to exploiting its ribonuclease capacity, Ribonuclease T2 (RNASET2) has been reported to exert anti-angiogenic and anti-tumorigenic effects in several tumors. However, the role of RNASET2 in gastric adenocarcinoma (GAC) remains unclear. The purpose of this study was to explore the expression, location, and clinical implications of RNASET2 in GAC. Methods: Data of RNASET2 mRNA expression in GAC and normal gastric mucosa tissues were extracted from three GSE series and 388 TCGA samples and reanalyzed. Genome-wide CRISPR/Cas9 proliferation screening datasets were used to investigate cell growth changes after RNASET2 knockout in 19 GAC cell lines. The biological processes involved in RNASET2 were studied by the bioinformatics analysis. Furthermore, the corresponding experiments including immunohistochemical staining, clinicopathological features analysis, survival curve, microvessel density detection, cell viability assay, and colony formation assay were performed to validate the expression and function of RNASET2 in GAC. Results: An abundance of RNASET2 was present in the fundus glands and pylorus glands of the normal gastric mucosa. RNASET2 mRNA and protein were down-regulated in GAC compared with adjacent non-cancerous or normal gastric mucosa tissues. The expression of RNASET2 mRNA and protein in early GAC was higher than that in advanced GAC. 79/134 gene sets involved in the early GAC pathway were enriched in the RNASET2 mRNA high expression group. Genome-wide shRNA and CRISPR/Cas9 proliferation screening showed that knockdown or knockout of RNASET2 could not significantly promote GAC cell growth. AlamarBlue cell viability assay and colony formation assay in AGS cells further validated these results. Clinicopathologic features and survival analysis demonstrated that RNASET2 protein was significantly correlated with tumor cell differentiation, Lauren's classification, and TM4SF1 protein expression, but not correlated with lymph nodal metastasis and patient's prognosis. Microvessel density detection indicated that no significant correlation was found between the expression of RNASET2 protein and the angiogenesis of GAC. Conclusions: Down-regulation of RNASET2 in GAC was only the consequence of the GAC, instead of the driver. The expression of RNASET2 could be regarded as a good biomarker for identifying the early stage of GAC.

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The meta and bioinformatics analysis of GRP78 expression in gastric cancer.

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The meta and bioinformatics analysis of GRP78 expression in gastric cancer.

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